Abstract
Lamprey immune protein (LIP), a novel protein derived from the Lampetra japonica, has been shown to exert efficient tumoricidal actions without concomitant damage to healthy cells. Our study aimed to ascertain the mechanisms by which LIP inhibits lung cancer cells, thus delineating potential innovative therapeutic strategies. LIP expression in lung cancer cells was evaluated by western blotting and immunohistochemistry. Functional assays, such as high-content imaging, 3D-structured illumination microscopy (3D-SIM) imaging, flow cytometry, and confocal laser scanning microscopy, were performed to examine the proliferation and lung cancer cell apoptosis. Tumor xenograft assays were performed using an in vivo imaging system. We observed that LIP induces the decomposition of certain lung cancer cell membranes by destroying organelles such as the microtubules, mitochondria, and endoplasmic reticulum (ER), in addition to causing leakage of cytoplasm, making the maintenance of homeostasis difficult. We also demonstrated that LIP activates the ER stress pathway, which mediates lung cancer cell apoptosis by producing reactive oxygen species (ROS). In addition, injection of LIP significantly retarded the tumor growth rate in nude mice. Taken together, these data revealed a role of LIP in the regulation of lung cancer cell apoptosis via control of the ER stress signaling pathway, thus revealing its possible application in lung cancer treatment.
Highlights
Lung cancer is the most common cause of cancer-related mortality worldwide, accounting for nearly 20% of all cancer deaths [1, 2]
propidium iodide (PI) staining was denoted by red, while Hoechst 33342 staining was denoted by blue
The results obtained after incubation of the three cell lines with different concentrations of Lamprey immune protein (LIP) for 24 h are shown in Figure 1C (n = 3)
Summary
Lung cancer is the most common cause of cancer-related mortality worldwide, accounting for nearly 20% of all cancer deaths [1, 2]. Human small-cell lung cancer, and human lung squamous cell carcinoma are the three common subtypes of lung cancer. Immunotherapy has played a pivotal role in the treatment of lung cancer. Lamprey Immune Protein Mediates Apoptosis efficacy in a small group of patients, in whom the tumor cells expressed high levels of the programmed cell death-ligand 1 (PD-L1) protein [4]. Despite considerable breakthroughs in targeted therapy over recent years, a large proportion of lung cancer patients are compelled to undergo traditional chemotherapy and radiotherapy, resulting in a five-year survival rate of
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